Wiskott-AIdrich syndrome protein regulates podosomes in primary human macrophages

摘要

Wiskott-Aldrich syndrome protein cyASp) is a hematopoictic-specific, multidomain protein whose mu- tation is responsible for the immunodeficiency disorder Wis. kott-AIdrich syndrome. WASP contains a binding motiffor tbe Rho GTPase CDC42Hs as well as verprolin/cofilin-like actin- regulatory domains, but no specific actin structure regulated by CDC42Hs-WASp has been identified. We found that WASP colocalizes with CDC42Hs and actin in the core of podosomes, a highly dynamic adhesion structure of human blood-derived macrophages. Microinjection of constitutively active V12CDC42Hs or a constitutively active WASP fragment con- sisting of the verprolin/cofilin-like domains led to the disas- semly or podosomes. Conversely, macrophages from patients expressing truncated forms of WASP completely lacked po- dosomes. These findings indicate that WASP controls podo- some assemhly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages.